Eosinophils are predominantly tissue-dwelling cells (spleen, lymph nodes, thymus,
digestive tract) and counts <500/mm3 in the peripheral blood are considered to
be normal. The functions of eosinophils are not completely understood, however
there can be a significant rise in their levels in the peripheral blood and/or tissues
in a variety of disease states. Hypereosinophilic syndromes (HES) are a group
of disorders characterised by blood eosinophilia greater than 1500/mm3 on at
least two occasions and eosinophilic infiltration and damage to multiple organs.
Eosinophils on activation release substances that can lead to tissue damage.
However, it is important to note that the degree of tissue damage is not directly
proportional to the level of eosinophilia. A significant number of cases of HES are
commonly missed and therefore a systematic approach is necessary for all such
patients. Through our case, we have tried to summarise how to systematically
approach a case of HES and manage it.

Our case was a 35 year old male,
resident of Bihar, India, who
presented to us with complaints of
on and off fever, generalised rash,
shortness of breath and loose stools for
the last 3-4 years.

The patient was apparently well till
around 4 years back when he started
having fever; which was intermittent,
low-moderate in intensity, without any
recognizable pattern, associated with
chills but no rigors and responded to
anti-pyretics. For this complaint he
had consulted local doctors and was
told to have enteric fever on multiple
occasions and was prescribed multiple
courses of antibiotics for the same,
without any strong evidence in favour
of the diagnosis (review of records
showed only weakly positive Widal
titres). Records also showed persistent
eosinophilia and anaemia which was attributed to worm infestation and
was treated with albendazole on
multiple occasions. However, 3 months
after onset of fever, the patient also
developed generalised maculo-papular
rashes over body and extremities,
which were mildly itchy but not
associated with scaling or any serous/
purulent discharge. The rashes used
to come in crops, responded to antihistaminics
and usually healed with
hyperpigmentation.

At a r ound the same time of
development of rash, the patient also
developed complaints of shortness of
breath which was insidious in onset and
gradually progressive. It was associated
with wheezing and was worse early in
the morning and during the winters.
It was also associated with cough and
scanty mucoid expectoration. There
was however, no history suggestive
of paroxysmal nocturnal dyspnea,
orthopnea, exertional chest pain,
palpitations or syncope.

Around 1 week after developing
rash and shortness of breath, he also
developed complaints of loose stools
which were of large volume, watery
in consistency, without pus or blood
or mucus. The frequency was around
3-4 times/day. There was mild diffuse
abdominal pain, loss of appetite without
any no history of vomiting. He had also lost significant body weight (around 18
kgs) in the last 4 years.

There was no history of any
recurrent oral ulcers, photosensitivity,
joint pains or painful paraesthesia.
There was no history suggestive of
any thrombotic events in the past. The
patient otherwise had no history of any major illness in the past except for
occasional allergic rhinitis, otitis media
or sinusitis. There was no history of
similar illness in his family. He was
married with one child and had no
addictions. He had also availed of
alternative medications occasionally
since there was no improvement in
his clinical condition over these many years. There was no history of intake
of drugs that are commonly associated
with eosinophilia (Table 1).1

On examination, the patient was
conscious and oriented. He was
hemodynamically stable without
any respiratory distress at rest. No
orthostatic hypotension was present.
Mild pallor was present. There were
few hyperpigmented macular lesions
all over his body; however, there was
no generalised hyperpigmentation.
Mid and lower jugular lymph nodes
approximately 1 cm x 1.5 cm were
palpable bilaterally. The patient was
febrile to touch. The ear-nose-throat
examination was unremarkabl e .
Respiratory system examination
revealed bilateral diffuse rhonchi with
prolonged expiration and occasional
crepitations. There was diffuse
tenderness all over the abdomen. Liver
was enlarged and the splenic tip was
palpable. Cardiovascular and nervous
system examination was normal.
With this clinical picture and a
background of persistently elevated
eosinophil counts , differential
diagnoses of persistent parasi t i c
infestation, Churg-Strauss syndrome,
hemtological malignancies and hypereosinophilic
syndrome (HES) amongst others (Table 2) were kept.2-4

Initial investigations included a
complete blood count which revealed
a total leucocyte count of 23000 cells/
mm3 with 37% eosinophils. Peripheral
blood smear showed no atypical cells or
parasites but microcytic hypochromic
anemia was present. ESR and CRP
were mildly elevated. The renal and
liver function tests were normal.
Urine examination did not reveal any
proteinuria or any active sediments.
Stool examination showed few pus
cells without any blood and culture was
negative. No parasites were identified.
Strongyloides serology came out to
be negative. The sputum examination
showed few pus cells but no pathogens
were grown on culture. AFB smear of
sputum was negative.

His ANCA was negative and Nerve
conduction studies were normal. There
was only mild bilateral maxillary
sinusitis on CT of para nasal sinuses.
No active skin lesion, suggestive
of vasculitis was present. Work up
for Allergic Bronchopulmonary
Aspergillosis (ABPA) was negative.

Since the primary work up for
the common causes was negative, a
bone marrow examination was done
which revealed a cellular marrow with
increased eosinophils and eosinophil
precursors. He was further evaluated to
look for the other causes of secondary
HES. Since HES may be associated with
myeloproliferative disorders, PDGFRA
and PDGFRB (platelet-derived growth factor) mutation, BCR:ABL and JAK
Kinase mutation studies were done,
which were all negative. His vitamin
B12 and serum tryptase levels, that
are also strongly associated with
myeloid variants of HES, were normal.
The other possibility kept in was the
lymphoid variant of HES; since skin
manifestations were predominant,
serum IgE levels were high and the
causes associated with myeloid variants
were ruled out. A peripheral blood
flow cytometry was done to look for
any T-cell abnormalities. The flow
cytometry results came out to be normal.
A transbronchial lung biopsy, from
left upper lobe, was done which was
showed features suggestive of chronic
interstitial pneumonia, eosinophilia
and interstitial fibrosis (Figure 2).
A duodenal biopsy was also done
which showed chronic inflammatory
changes with eosinophilic infiltration.
A summary of all the investigations has
been listed in Table 4.

The patient fulfilled the criteria for
and was finally labelled as a case of
idiopathic HES (Table 5).8

HES can be of various types (Table
6) and an approach to a case of HES is
summarised in Figure 3. Identification
of the underlying condition is important
as it significantly changes the treatment
strategy and the prognosis of the
patients.

An extensive review of literature
confirmed that the available options
for the same in eosinophilia were
limited (Figure 4).9-11 The patient was
started on prednisone at 1mg/kg/day
in view of persistent eosinophilia
and organ involvement. The patient
became afebrile on the next day
and eosinophilia rapidly declined
to 2700/mm3 from 8510/mm3 in 24
hours. Eosinophil counts completely
normalised in 5 days. His shortness
of breath, gastro-intestinal complaints
and skin rash also resolved. The patient
was discharged on prednisone. Oral
iron supplementation was done for iron deficiency anaemia.

The patient is on regular follow up
and doing well at a maintenance dose
of 10mg of prednisolone per day.

Conclusion

It is important to systematically
approach a case of eosinophilia
to establish the proper etiological
diagnosis. Idiopathic hypereosinophilic
syndrome is diagnosed after ruling
out the other common causes and its mainstay of treatment is steroids.